Mechanism of Action
Like the structurally related thiazide diuretics, xipamide acts on the kidneys to reduce sodium reabsorption in the distal convoluted tubule. This increases the osmolarity in the lumen, causing less water to be reabsorbed by the collecting ducts. This leads to increased urinary output. Unlike the thiazides, xipamide reaches its target from the peritubular side (blood side).
Additionally, it increases the secretion of potassium in the distal tubule and collecting ducts. In high doses it also inhibits the enzyme carbonic anhydrase which leads to increased secretion of bicarbonate and alkalizes the urine.
Unlike with thiazides, only terminal renal failure renders xipamide ineffective.
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